Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.

Abstract

5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.

• Authors: Carolina Didonet Pederzolli, Caroline Paula Mescka, Bernardo Remuzzi Zandoná, Daniella de Moura Coelho, Angela Malysz Sgaravatti, Mirian Bonaldi Sgarbi, Angela Terezinha de Souza Wyse, Clóvis Milton Duval Wannmacher, Moacir Wajner, Carmen Regla Vargas, Carlos Severo Dutra-Filho
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 25 Issue 2 Pg. 145-54 (Jun 2010) ISSN: 1573-7365 [Electronic] United States
• PMID: 20431931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Nerve Tissue Proteins
• Glutathione Synthase
• Pyrrolidonecarboxylic Acid

Topics

• Age Factors
• Animals
• Antioxidants (metabolism, physiology)
• Brain Diseases, Metabolic, Inborn (chemically induced, metabolism)
• Cerebellum (drug effects, metabolism)
• Cerebrum (drug effects, metabolism)
• Disease Models, Animal
• Glutathione Synthase (deficiency)
• Lipid Peroxidation (drug effects, physiology)
• Nerve Tissue Proteins (metabolism, physiology)
• Oxidative Stress (drug effects, physiology)
• Pyrrolidonecarboxylic Acid (metabolism, toxicity)
• Rats
• Rats, Wistar